CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Newly Diagnosed High-Risk Multiple Myeloma: Outcomes and Management.
Newly Diagnosed High-Risk Multiple Myeloma: Outcomes and Management.
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多发性骨髓瘤(MM)是一种异质性血液系统恶性肿瘤;del(17p)、t(4;14)、t(14;16)和gain(1q)等高危细胞遗传学异常,约见于20%–25%的新诊断患者,并导致预后不良。这些异常与疾病侵袭性强、频繁复发以及较差的无进展生存期和总生存期相关。本综述探讨高危MM不断发展的治疗格局,重点关注适合和不适合移植患者的诱导治疗策略、自体干细胞移植(ASCT)的作用,以及巩固和维持治疗。文章还考察双特异性抗体和CAR-T 细胞等新兴疗法,尤其是将其前移至更早治疗线次的可能性。包含蛋白酶体抑制剂、免疫调节药物和单克隆抗体的四药诱导方案显示出改善结局的潜力,正逐渐成为一线治疗基石。本综述还强调,依据细胞遗传学谱和微小残留病(MRD)监测实施个体化、风险适配策略具有重要潜力。目前评估早期应用CAR-T 和双特异性抗体的临床试验,可能进一步改变高危MM患者的标准治疗。
Multiple myeloma (MM) is a heterogeneous hematologic malignancy, with high-risk cytogenetic abnormalities (HRCAs) such as del(17p), t(4; 14), t(14; 16), and gain(1q) contributing to poor prognosis in approximately 20%-25% of newly diagnosed patients. These abnormalities are associated with aggressive disease, frequent relapses, and inferior progression-free and overall survival. This review explores the evolving therapeutic landscape for high-risk MM, focusing on induction strategies for both transplant-eligible and transplant-ineligible patients, the role of autologous stem cell transplantation (ASCT), and the use of consolidation and maintenance therapies.
Emerging modalities such as bispecific antibodies and chimeric antigen receptor T-cell (CAR-T) therapies are examined, particularly in the context of their integration into earlier lines of treatment. Quadruplet induction regimens incorporating proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies have shown promise in improving outcomes and are becoming a cornerstone of frontline therapy.
The review also emphasizes the potential of personalized, risk-adapted approaches based on cytogenetic profiling and minimal residual disease (MRD) monitoring. Ongoing clinical trials investigating the early use of CAR-T cells and bispecific antibodies may further transform the standard of care for patients with high-risk MM.
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